title: A Mendelian predisposition to B-cell lymphoma caused by IL-10R deficiency.
abstract: Monogenic interleukin-10 (IL-10) and IL-10 receptor (IL-10R) deficiencies cause very early onset severe inflammatory bowel disease. Here, we report that 5 patients with an IL-10R1 (n = 1) or IL-10R2 (n = 4) deficiency developed B-cell non-Hodgkin lymphoma between the ages of 5 and 6 years (which was recurrent in 1 patient). These lymphomas had some of the characteristics of diffuse large B-cell lymphomas and contained monoclonal, Epstein-Barr virus-negative germinal center B cells. The tumors displayed a remarkably homogeneous signature, with original activation of the nuclear factor κB pathway and a decrease in intratumor T-cell infiltration. Hence, IL-10R deficiency is associated with a high risk of developing B-cell lymphoma. Our results revealed an unexpected role of the IL-10R pathway in lymphomagenesis.
authors.affiliation: Unité d'immuno-hématologie pédiatrique, Hôpital Necker-Enfant Malades, Assistance Publique des Hôpitaux de Paris (APHP), Paris, France;
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Neven
authors.forename: Emilie
authors.initials: E
authors.lastname: Mamessier
authors.forename: Julie
authors.initials: J
authors.lastname: Bruneau
authors.forename: Sophie
authors.initials: S
authors.lastname: Kaltenbach
authors.forename: Daniel
authors.initials: D
authors.lastname: Kotlarz
authors.forename: Felipe
authors.initials: F
authors.lastname: Suarez
authors.forename: Julien
authors.initials: J
authors.lastname: Masliah-Planchon
authors.forename: Katy
authors.initials: K
authors.lastname: Billot
authors.forename: Danielle
authors.initials: D
authors.lastname: Canioni
authors.forename: Pierre
authors.initials: P
authors.lastname: Frange
authors.forename: Isabelle
authors.initials: I
authors.lastname: Radford-Weiss
authors.forename: Vahid
authors.initials: V
authors.lastname: Asnafi
authors.forename: Dhaarini
authors.initials: D
authors.lastname: Murugan
authors.forename: Christine
authors.initials: C
authors.lastname: Bole
authors.forename: Patrick
authors.initials: P
authors.lastname: Nitschke
authors.forename: Olivier
authors.initials: O
authors.lastname: Goulet
authors.forename: Jean-Laurent
authors.initials: JL
authors.lastname: Casanova
authors.forename: Stéphane
authors.initials: S
authors.lastname: Blanche
authors.forename: Capucine
authors.initials: C
authors.lastname: Picard
authors.forename: Olivier
authors.initials: O
authors.lastname: Hermine
authors.forename: Frederic
authors.initials: F
authors.lastname: Rieux-Laucat
authors.forename: Nicole
authors.initials: N
authors.lastname: Brousse
authors.forename: Frederic
authors.initials: F
authors.lastname: Davi
authors.forename: Véronique
authors.initials: V
authors.lastname: Baud
authors.forename: Christoph
authors.initials: C
authors.lastname: Klein
authors.forename: Bertrand
authors.initials: B
authors.lastname: Nadel
authors.forename: Frank
authors.initials: F
authors.lastname: Ruemmele
authors.forename: Alain
authors.initials: A
authors.lastname: Fischer
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D005260:Female; D020869:Gene Expression Profiling; D020573:Genes, rel; D020022:Genetic Predisposition to Disease; D018858:Germinal Center / Q000276:immunology / Q000473:pathology; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000150:complications / Q000235:genetics / Q000276:immunology; D016753:Interleukin-10 / Q000378:metabolism; D053709:Interleukin-10 Receptor alpha Subunit / Q000172:deficiency* / Q000235:genetics*; D053710:Interleukin-10 Receptor beta Subunit / Q000172:deficiency* / Q000235:genetics*; D016393:Lymphoma, B-Cell / Q000209:etiology / Q000235:genetics* / Q000276:immunology*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000209:etiology / Q000235:genetics / Q000276:immunology; D008297:Male; D009154:Mutation; D016328:NF-kappa B / Q000378:metabolism; D010375:Pedigree; D015398:Signal Transduction
chemical_list: C508609:IL10 protein, human; D053709:Interleukin-10 Receptor alpha Subunit; D053710:Interleukin-10 Receptor beta Subunit; D016328:NF-kappa B; D016753:Interleukin-10